Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance

Completed

• Conditions: SCLC,Extensive Stage
• Interventions: Drug: PD-(L)1 antibody immunotherapy

• Registration Number: NCT05933863
• Lead Sponsor: Peking University Cancer Hospital & Institute

Brief Summary

To validate the predictive value of transcriptome-based molecular subtyping of extensive stage small cell lung cancer (SCLC) for the efficacy of programmed death-1(PD-1)/programmed death-ligand1(PD-L1) inhibitor in the first line setting; to explore the differences of immune microenvironment between different SCLC subtypes to reveal the mechanisms of immunotherapy resistance of SCLC

Detailed Description

This retrospective observational study examines the predictive value of transcriptome-based molecular subtyping of extensive stage SCLC for PD-1/PD-L1 inhibitor efficacy and explores immune microenvironment differences between subtypes to uncover immunotherapy resistance mechanisms. Patients with extensive stage SCLC receiving first-line standard treatment are enrolled, and baseline tumor tissue and peripheral blood samples are collected for transcriptome sequencing and immunohistochemistry (IHC). Based on results, patients are classified into four molecular subtypes, and treatment efficacy and safety are recorded. The study compares the efficacy between SCLC subtypes to determine if molecular typing predicts immunotherapy efficacy and investigates immune microenvironment differences between subtypes to uncover resistance mechanisms. Treatment regimens follow first-line extensive stage SCLC guidelines, including cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitors, with options determined by the supervising physician.

Study Timeline

• Study Start: 2022-03-29
• Study First Submitted: 2023-06-24
• Study First Submitted QC: 2023-07-03
• Study First Posted: 2023-07-06
• Primary Completion: 2024-07-18
• Status Verified: 2024-11
• Study Completion: 2024-12-01
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

Inclusion Criteria

• The enrolled subjects shall meet all the following conditions at the same time.

  1. Male or female, aged 18 to 100 years
  2. Patients with untreated advanced small cell lung cancer clearly diagnosed by histopathology
  3. Be able to provide tumor biopsy tissue sample for molecular analysis
  4. Eastern Cooperative oncology Group (ECOG) score: 0~2
  5. Expected survival of more than 3 months.
  6. Has at least 1 measurable or evaluable tumor lesion with a longest diameter ≥ 10 mm at baseline (in case of lymph nodes, a shortest diameter ≥ 15 mm is required) according to RECIST v1.1
  7. Received first-line chemotherapy or chemotherapy＋PD-(L)1 inhibitor and be able to provide complete treatment information and efficacy evaluation results.
  8. Voluntary signed informed consent and expected good compliance.

Exclusion Criteria

• Those meeting any of the following conditions may not be included.

  1. Patient unable to tolerate chemotherapy.
  2. Patients unable to provide tumor tissue samples for testing
  3. Patients with other malignant tumors or a history of other malignant tumors
  4. Patients have any other reason to be unfit to participate in this study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
immunotherapy cohort	PD-(L)1 antibody immunotherapy	Extensive stage SCLC patients receiving first-line chemotherapy plus PD-(L)1 antibody treatment will be enrolled in this cohort. Baseline tumor tissue samples and peripheral blood samples will be collected for transcriptome and immunohistochemistry analysis etc.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	2022.4.1-2023.12.31	From the start of first-line treatment until disease progression or death due to any cause

Secondary Outcome Measures

Name	Time	Method
molecular subtyping and tumor microenvironment biomarkers	2022.4.10-2023.12.31	The molecular subtyping was carried out based on transcripsome sequencing following the method in published article PMID: 33482121, the tumor microenvironment biomarkers include tumor infiltrated immune cells and specific gene expression evaluated by transcripsome and Multiplex immunohistochemical analysis etc.
Overall survival	2022.4.10-2024.12.31	From the start of first-line treatment until death due to any cause
Objective response rate	2022.4.10-2023.12.31	The tumor size was calculated by computed tomography or magnetic resonance Imaging scan, the best response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECISTVersion1.1)

Trial Locations

Locations (1)

Peking University Cancer Hospital & Institute; 🇨🇳 Beijing, Beijing, China